Heterogeneity in bladder cancer as detected by conventional chromosome analysis and interphase cytogenetics

Schapers, R.F.M.; Smeets, Wim; Hopman, Anton H. N.; Pauwels, R.P.E.; Geraedts, J. P. M.; Ramaekers, F.

doi:10.1016/0165-4608(93)90131-5

Cited by 13 publications

(10 citation statements)

References 13 publications

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“…Histological and genetic heterogeneity is well documented in TCCs [2,5,28,56,63,67]. After malignant transformation, tumor cells can grow independently with variable subsequent genetic alterations in each tumor com-290 Fig.…”

Section: Intratumor Heterogeneity: Correlation Between Molecular and mentioning

confidence: 99%

Molecular and kinetic features of transitional cell carcinomas of the bladder: biological and clinical implications

et al. 2001

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Molecular and kinetic analyses have contributed to our understanding of the biology of transitional cell carcinomas (TCC) of the bladder. The concordant pattern of X-chromosome inactivation of multiple TCCs appearing at different times and at different sites and concordant genetic abnormalities in a subset of muscle-invasive TCC strongly support a monoclonal origin and a homogeneous tumor cell selection throughout the neoplasm. However, topographic intratumor heterogeneity results from the accumulation of genetic lesions in tumor suppressor genes, predominantly neurofibromatosis (NF)-1-defective in the superficial compartment and tumor protein p53 (TP53)-defective in the deep one, with lower proliferation and down-regulation of apoptosis in the latter. TCCs follow the general concept of multistep carcinogenesis and proceed through two distinct genetic pathways responsible for generating different TCC morphologies. These are the inactivation of cyclin-dependent kinase inhibitors (p15, p16, and p21WAF/CIP1) in low-grade TCC and early TP53-mediated abnormalities in high-grade TCC. TCC progression correlates with genetic instability and accumulation of collaborative genetic lesions mainly involving TP53, retinoblastoma (RB)-1, and growth factors. Distinctive genetic (low incidence of RB-1 and NF-1 abnormalities) and kinetic (slower cell turnover) profiles also correlate with a "single-file" infiltration pattern and poor survival in muscle-invasive TCCs. The underlying molecular changes of carcinoma in situ involve multiple and more extensive deletions (normally TP53-defective) than coexistent invasive TCC, suggesting an independent genetic evolution, while low-grade dysplasia is mainly polyclonal and shows a low rate of gene deletions.

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Section: Intratumor Heterogeneity: Correlation Between Molecular and mentioning

confidence: 99%

Molecular and kinetic features of transitional cell carcinomas of the bladder: biological and clinical implications

et al. 2001

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“…Flow cytometry has been found to be less sensitive in detecting abnormalities in TCC. An abnormal DNA content has been reported in 9-13% of Ta tumours and 47-57% of pT1 tumours [3,20,25]. FISH has demonstrated characteristic chromosomal aberrations in T1 tumours relative to Ta tumours [23].…”

Section: Discussionmentioning

confidence: 96%

“…Chromosomal aberrations have been found in 47-100% of tumours, depending on the tumour stage [15]. Tumours that are diploid by FCM prove to have chromosomal aberrations in about 60% of cases with FISH [19,20].…”

Section: Introductionmentioning

confidence: 98%

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Abnormalities detected in metaphase chromosomes in bladder carcinoma: prognostic value and comparison with histopathological factors

Oosterhuis¹,

Smeets²,

Janssen‐Heijnen

et al. 2002

Virchows Arch

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The objective of this study was to detect the incidence and prognostic value of chromosomal aberrations in metaphase chromosomes (hypodiploidy, hyperdiploidy and/or structural abnormalities) in Ta and T1 transitional cell carcinoma (TCC) of the bladder. Of 266 patients, the metaphase chromosomes of the primary tumour were studied using a direct microscopic analysis and classified into two categories: normal and abnormal. Recurrence and progression were prospectively recorded during a median follow-up period of 40 months and in a retrospective analysis compared with other prognostic factors. Chromosomal abnormalities were found in 48% of Ta tumours and in 92% of T1 tumours. In univariate analysis, chromosomal abnormalities were associated with recurrence-free survival ( P=0.03) and progression-free survival ( P=0.01). In multivariate analysis, chromosomal abnormalities (RR=1.98) and age (RR=0.64) were independent predictors of recurrence-free survival but not progression-free survival.

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“…Likewise, FCM DNA studies of multiple samples from different sites in one tumor and/or metastases have shown heterogeneity in DNA in lung cancers (7,38), gliomas (lo), pancreatic tumors (39), gastrointestinal cancers ( 11,38), and ovarian carcinomas ( 15). In addition, in epithelial tumors such as bladder cancer (19,20,35), breast cancer ( 1 2 ) , and lung cancer ( 2 2 ) , cytogenetic heterogeneity has been revealed by interphase cytogenetics.…”

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confidence: 99%

Cytogenetic heterogeneity and histologic tumor growth patterns in prostatic cancer

et al. 1995

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Twenty-five prostatic adenocarcinomas were studied for the presence of intratumoral cytogenetic heterogeneity by interphase in situ hybridization (ISH) to routinely processed tissue sections. ISH with a chromosome Y-specific repetitive DNA probe provided a model to investigate patterns of chromosomal heterogeneity within and between different pathological grades. The Gleason grading system was used, since it is based on a detailed classification of growth patterns. Heterogeneity with respect to ploidy of the tumor was examined by ISH with a repetitive DNA probe specific for chromosome 1. The ploidy status of these cancers was confirmed by DNA flow cytometry (P < 0.001). Cytogenetic heterogeneity at the (Y) chromosomal level was observed between Gleason areas, within one area, and even within single tumor glands. The different patterns of chromosomal heterogeneity were seen in all tumor grades and stages. Differences in ploidy status were also found following the aforementioned histological patterns, again, in all grades and stages. Intraglandular heterogeneity was most frequently seen. No correlation was found between cytogenetic heterogeneity and proliferative activity . In contrast to current views on clonality, suggesting regional separation of subclones with different DNA content, this study demonstrates that these subclones can be interspersed. o 1995 wiley-Liss, h c .

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Heterogeneity in bladder cancer as detected by conventional chromosome analysis and interphase cytogenetics

Cited by 13 publications

References 13 publications

Molecular and kinetic features of transitional cell carcinomas of the bladder: biological and clinical implications

Molecular and kinetic features of transitional cell carcinomas of the bladder: biological and clinical implications

Abnormalities detected in metaphase chromosomes in bladder carcinoma: prognostic value and comparison with histopathological factors

Cytogenetic heterogeneity and histologic tumor growth patterns in prostatic cancer

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